Maternal E-cigarette Use Can Disrupt Postnatal Blood-brain Barrier (BBB) Integrity and Deteriorates Motor, Learning and Memory Function: Influence of Sex and Age

Overview

Journal Fluids Barriers CNS

Publisher Biomed Central

Date 2023 Mar 10

PMID 36899432

Authors

Sabrina Rahman Archie

Ali Ehsan Sifat

Yong Zhang

Heidi Villalba

Sejal Sharma

Saeideh Nozohouri

Thomas J Abbruscato

Affiliations

Soon will be listed here.

Abstract

Electronic nicotine delivery systems (ENDS), also commonly known as electronic cigarettes (e-cigs) are considered in most cases as a safer alternative to tobacco smoking and therefore have become extremely popular among all age groups and sex. It is estimated that up to 15% of pregnant women are now using e-cigs in the US which keeps increasing at an alarming rate. Harmful effects of tobacco smoking during pregnancy are well documented for both pregnancy and postnatal health, however limited preclinical and clinical studies exist to evaluate the long-term effects of prenatal e-cig exposure on postnatal health. Therefore, the aim of our study is to evaluate the effect of maternal e-cig use on postnatal blood-brain barrier (BBB) integrity and behavioral outcomes of mice of varying age and sex. In this study, pregnant CD1 mice (E5) were exposed to e-Cig vapor (2.4% nicotine) until postnatal day (PD) 7. Weight of the offspring was measured at PD0, PD7, PD15, PD30, PD45, PD60 and PD90. The expression of structural elements of the BBB, tight junction proteins (ZO-1, claudin-5, occludin), astrocytes (GFAP), pericytes (PDGFRβ) and the basement membrane (laminin α1, laminin α4), neuron specific marker (NeuN), water channel protein (AQP4) and glucose transporter (GLUT1) were analyzed in both male and female offspring using western blot and immunofluorescence. Estrous cycle was recorded by vaginal cytology method. Long-term motor and cognitive functions were evaluated using open field test (OFT), novel object recognition test (NORT) and morris water maze test (MWMT) at adolescence (PD 40-45) and adult (PD 90-95) age. In our study, significantly reduced expression of tight junction proteins and astrocyte marker were observed in male and female offspring until PD 90 (P < 0.05). Additionally, prenatally e-cig exposed adolescent and adult offspring showed impaired locomotor, learning, and memory function compared to control offspring (P < 0.05). Our findings suggest that prenatal e-cig exposure induces long-term neurovascular changes of neonates by disrupting postnatal BBB integrity and worsening behavioral outcomes.

Citing Articles

The effects of flavored vaped e-liquids on cultured human macrophages derived from the central and peripheral nervous systems.

Bradley C, Walker-Franklin I, Kovach A, Sivaraman V, Onyenwoke R Toxicol In Vitro. 2025; 104:106013.

PMID: 39894183 PMC: 11845287. DOI: 10.1016/j.tiv.2025.106013.

Influence of gestational window on offspring vascular health in rodents with in utero exposure to electronic cigarettes.

Mills A, Nassabeh S, Hurley A, Shouldis L, Chantler P, Dakhlallah D J Physiol. 2024; 602(17):4271-4289.

PMID: 39106241 PMC: 11376404. DOI: 10.1113/JP286493.

Maternal use of electronic cigarettes and impact on offspring: a double-hit model.

Mills A, Velayutham M, Corbin D, Suter L, Robinson M, Khramtsov V J Appl Physiol (1985). 2024; 137(3):690-704.

PMID: 39088647 PMC: 11424175. DOI: 10.1152/japplphysiol.00345.2024.

The Acute Impact of Propofol on Blood-Brain Barrier Integrity in Mice.

Nozohouri E, Ahn Y, Zoubi S, Patel D, Archie S, Akter K Pharm Res. 2024; 41(8):1599-1611.

PMID: 39044046 DOI: 10.1007/s11095-024-03735-w.

Altered insular functional activity among electronic cigarettes users with nicotine dependence.

Sun Y, Xie A, Fang Y, Chen H, Li L, Tang J Transl Psychiatry. 2024; 14(1):293.

PMID: 39019862 PMC: 11255336. DOI: 10.1038/s41398-024-03007-6.

References

Bosworth A, Allen N . The diverse actions of astrocytes during synaptic development. Curr Opin Neurobiol. 2017; 47:38-43. DOI: 10.1016/j.conb.2017.08.017. View

Zlokovic B . The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008; 57(2):178-201. DOI: 10.1016/j.neuron.2008.01.003. View

Abbruscato T, Lopez S, Mark K, Hawkins B, Davis T . Nicotine and cotinine modulate cerebral microvascular permeability and protein expression of ZO-1 through nicotinic acetylcholine receptors expressed on brain endothelial cells. J Pharm Sci. 2002; 91(12):2525-38. DOI: 10.1002/jps.10256. View

Caldarone B, King S, Picciotto M . Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice. Neurosci Lett. 2008; 439(2):187-91. PMC: 2491450. DOI: 10.1016/j.neulet.2008.05.023. View

Balbuena P, Li W, Ehrich M . Assessments of tight junction proteins occludin, claudin 5 and scaffold proteins ZO1 and ZO2 in endothelial cells of the rat blood-brain barrier: cellular responses to neurotoxicants malathion and lead acetate. Neurotoxicology. 2010; 32(1):58-67. DOI: 10.1016/j.neuro.2010.10.004. View

Gustavson K, Ystrom E, Stoltenberg C, Susser E, Suren P, Magnus P . Smoking in Pregnancy and Child ADHD. Pediatrics. 2017; 139(2). PMC: 5260151. DOI: 10.1542/peds.2016-2509. View

Villalba H, Shah K, Albekairi T, Sifat A, Vaidya B, Abbruscato T . Potential role of myo-inositol to improve ischemic stroke outcome in diabetic mouse. Brain Res. 2018; 1699:166-176. DOI: 10.1016/j.brainres.2018.08.028. View

Alkam T, Kim H, Mamiya T, Yamada K, Hiramatsu M, Nabeshima T . Evaluation of cognitive behaviors in young offspring of C57BL/6J mice after gestational nicotine exposure during different time-windows. Psychopharmacology (Berl). 2013; 230(3):451-63. DOI: 10.1007/s00213-013-3175-9. View

Huang L, Wang Y, Zhang L, Zheng Z, Zhu T, Qu Y . Maternal Smoking and Attention-Deficit/Hyperactivity Disorder in Offspring: A Meta-analysis. Pediatrics. 2017; 141(1). DOI: 10.1542/peds.2017-2465. View

10.

Li H, Li X, Gao S, Wang D, Gao X, Li Y . Exposure to Cigarette Smoke Augments Post-ischemic Brain Injury and Inflammation via Mobilization of Neutrophils and Monocytes. Front Immunol. 2019; 10:2576. PMC: 6853894. DOI: 10.3389/fimmu.2019.02576. View

11.

Kaisar M, Villalba H, Prasad S, Liles T, Sifat A, Sajja R . Offsetting the impact of smoking and e-cigarette vaping on the cerebrovascular system and stroke injury: Is Metformin a viable countermeasure?. Redox Biol. 2017; 13:353-362. PMC: 5480985. DOI: 10.1016/j.redox.2017.06.006. View

12.

Nguyen T, Li G, Chen H, Cranfield C, McGrath K, Gorrie C . Maternal E-Cigarette Exposure Results in Cognitive and Epigenetic Alterations in Offspring in a Mouse Model. Chem Res Toxicol. 2018; 31(7):601-611. DOI: 10.1021/acs.chemrestox.8b00084. View

13.

Li Y, Wang F, Wang W, Luo Y, Wu P, Xiao J . Aquaporin-4 deficiency impairs synaptic plasticity and associative fear memory in the lateral amygdala: involvement of downregulation of glutamate transporter-1 expression. Neuropsychopharmacology. 2012; 37(8):1867-78. PMC: 3376319. DOI: 10.1038/npp.2012.34. View

14.

Julvez J, Ribas-Fito N, Torrent M, Forns M, Garcia-Esteban R, Sunyer J . Maternal smoking habits and cognitive development of children at age 4 years in a population-based birth cohort. Int J Epidemiol. 2007; 36(4):825-32. DOI: 10.1093/ije/dym107. View

15.

Liu B, Du Y, Wu Y, Sun Y, Santillan M, Santillan D . Prevalence and Distribution of Electronic Cigarette Use Before and During Pregnancy Among Women in 38 States of the United States. Nicotine Tob Res. 2021; 23(9):1459-1467. PMC: 8517965. DOI: 10.1093/ntr/ntab041. View

16.

Zhang Y, Archie S, Ghanwatkar Y, Sharma S, Nozohouri S, Burks E . Potential role of astrocyte angiotensin converting enzyme 2 in the neural transmission of COVID-19 and a neuroinflammatory state induced by smoking and vaping. Fluids Barriers CNS. 2022; 19(1):46. PMC: 9171490. DOI: 10.1186/s12987-022-00339-7. View

17.

Dwyer J, McQuown S, Leslie F . The dynamic effects of nicotine on the developing brain. Pharmacol Ther. 2009; 122(2):125-39. PMC: 2746456. DOI: 10.1016/j.pharmthera.2009.02.003. View

18.

Micalizzi L, Knopik V . Maternal smoking during pregnancy and offspring executive function: What do we know and what are the next steps?. Dev Psychopathol. 2017; 30(4):1333-1354. PMC: 6028309. DOI: 10.1017/S0954579417001687. View

19.

Orzabal M, Lunde-Young E, Ramirez J, Howe S, Naik V, Lee J . Chronic exposure to e-cig aerosols during early development causes vascular dysfunction and offspring growth deficits. Transl Res. 2019; 207:70-82. PMC: 6486852. DOI: 10.1016/j.trsl.2019.01.001. View

20.

Hughes E, Maguire J, McMinn M, Scholz R, Sutherland M . Loss of glial fibrillary acidic protein results in decreased glutamate transport and inhibition of PKA-induced EAAT2 cell surface trafficking. Brain Res Mol Brain Res. 2004; 124(2):114-23. DOI: 10.1016/j.molbrainres.2004.02.021. View